Abstract

NPM1 belongs to a new category of genes that function both as oncogenes and tumor suppressor genes, depending on gene dosage, expression levels, interacting partners, and compartmentalization. Nucleophosmin mutations within exon 12 have been described as the most frequent acquired molecular abnormalities in adult and pediatric acute myeloid leukaemia (AML), mutation can be observed in nearly half of patients with a normal karyotype and is associated with a favorable outcome. NPM1 mutations are characterized by the aberrant cytoplasmic localization of NPM, the absence of CD34, involvement of several cell lineages myeloid, monocytic, erythroid and megakaryocytic but not lymphoid and a high frequency of FLT3-ITD mutation. We aimed to study the prevalence, association with Flt3 mutations, and prognostic impact of NPM1 exon-12 mutations in 71 AML patients with normal karyotype. We studied NPM1 and FLT3 by RT PCR. NPM1 gene mutation was detected among 34 patients (47.9%) and was associated with a high white blood cell count, involvement of the monocytic lineage, CD34 negativity, and high frequency of FLT3ITD. DFS and OS did not differ between mutated and unmutated NPM patients. Prospective studies are needed to confirm the definitive place of NPM mutation among patients with normal karyotype.